...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human astrocytoma cells by the pyrrolo-1,5-benzoxazepine, PBOX-21
【24h】

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human astrocytoma cells by the pyrrolo-1,5-benzoxazepine, PBOX-21

机译：pyrrolo-1,5-benzoxazep​​ine，PBOX-21抑制人星形细胞瘤细胞生长停滞期间的G1细胞周期蛋白依赖性激酶活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The present study examines the molecular mechanisms by which a member of a novel series of pyrrolo-1,5-benzoxazepines, PBOX-21, induces G1 arrest in 1321N1 cells. PBOX-21-induced G1 arrest is preceded by both a decrease in CDK2 kinase activity, which is critical for the G1/S transition, and a downregulation in cyclin D_3 protein expression levels, suggesting that these two events may be crucially involved in the mediation of the cell cycle arrest. The decrease in CDK2 activity may be due to an observed decrease in CDK2 protein levels following PBOX-21 treatment. Coinciding with the arrest is a reduction in the activity of CDK4, due to either the observed PBOX-21 induced downregulation in CDK4 expression, or a reduction in complex formation between cyclin D_3-CDK4 leading to a decrease in the levels of active cyclin D_3-CDK4 complexes with kinase activity. The level of CDK6 activity was also seen to be reduced following PBOX-21 treatment, also possibly due to a reduction in complex formation with cyclin D_3. However, this reduction in CDK6 kinase activity was not seen until after PBOX-21-induced G1 arrest has reached its maximum, and therefore may be viewed as a consequence of, and a method of maintaining the PBOX-21-induced arrest, rather than a cause. Also in parallel with the G1 arrest elicited by PBOX-21 is an upregulation in the universal CDK inhibitor, p21. Furthermore, the retinoblastoma protein (Rb), a substrate of CDK2 and CDK6, whose phosphorylation is necessary for cell cycle progression becomes hypophosphorylated. These results indicate that PBOX-21 exerts its growth inhibitory effects through the modulation of the expression and activity of several key G1 regulatory proteins.
机译：本研究研究了一系列新的吡咯并-1,5-苯并x氮平成员PBOX-21诱导1321N1细胞中G1阻滞的分子机制。 PBOX-21诱导的G1阻滞伴随着CDK2激酶活性的下降（这对G1 / S过渡至关重要）和细胞周期蛋白D_3蛋白表达水平的下调，这提示这两个事件可能与调解至关重要细胞周期停滞。 CDK2活性的降低可能是由于观察到PBOX-21治疗后CDK2蛋白水平的降低。与逮捕相关的是，由于观察到的PBOX-21诱导的CDK4表达下调，或者由于细胞周期蛋白D_3-CDK4之间复杂形成的减少导致活性细胞周期蛋白D_3-水平的降低，CDK4的活性降低。具有激酶活性的CDK4复合物。在PBOX-21处理后，还发现CDK6活性水平降低，这也可能是由于细胞周期蛋白D_3的复合物形成减少。但是，直到PBOX-21诱导的G1阻滞达到最大后才观察到CDK6激酶活性的降低，因此，可以认为这是维持PBOX-21诱导的阻滞的一种方法的结果，而不是一个原因。与PBOX-21引起的G1阻滞同时出现的是通用CDK抑制剂p21的上调。此外，视网膜母细胞瘤蛋白（Rb），即CDK2和CDK6的底物，其磷酸化对于细胞周期的发展是必需的，被磷酸化。这些结果表明PBOX-21通过调节几种关键的G1调节蛋白的表达和活性发挥其生长抑制作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号